Normal lab values

Ideally, therapeutic goal should be measurement of brain lithium level, but additional research is needed to define the therapeutic brain lithium level and its clinical utility in treatment and overdose.

Lithium with complex and lengthy distribution time to target organs.

Toxicity often occurs when serum level is above therapeutic range, but considering complex distribution pharmacokinetics, clinical presentation is more important than serum level in considering treatment.

Level may continue to rise for more than a day after ingestion of a sustained-release product.

Serum lithium levels may not correlate well with CNS levels or toxicity after overdose.

Lithium elimination half-life is longer in the elderly and those taking lithium chronically.

Establishing the diagnosis

If patient has elevated serum lithium concentration without signs consistent with toxicity, consider (1) was sample collected prior to drug distribution out of serum and into large organs (CNS), and (2) was serum collected in lithiated-heparin tube, causing a false elevation in the reported lithium concentration.

Differential diagnosis

For chronic or acute-on-chronic toxicity

Note: Because lithium has a narrow therapeutic index, serum and CNS levels do not always correlate well. It may be especially difficult to distinguish patients who take lithium therapeutically and have meningitis with chronic lithium toxicity.

WBI decreases serum lithium levels after ingestion of sustained-release preparations and is recommended after a large overdose of this formulation if no contraindication exists (e.g., obstruction, ileus).

Serum lithium level expected to rebound within 6 - 8 hr after hemodialysis as lithium is drawn out of target tissues down its concentration gradient (goal of therapy). Therefore, repeat hemodialysis is often required.

Although a rough guideline of serum lithium concentration > 4.0 mmol/L in acute toxicity or > 2.5 mmol/L in chronic toxicity has been proposed, clinical status, not serum lithium concentration, should guide therapy.

Bicarbonate hemodialysis may prevent lithium being driven into cells by the sodium-hydrogen antiporter, as likely occurs during acetate hemodialysis.

In patients unable to tolerate hemodialysis due to hypotension, continuous veno-venous hemodialysis also effectively removes lithium, but at a slower continuous rate.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

Patients suffering from acute toxicity without whole body stores are expected to improve clinically rapidly (hours to days) with treatment.

Patients with whole body stores and an acute ingestion (acute-on-chronic toxicity) or chronic toxicity often take days to weeks to completely recover clinically.

Pathophysiology

Lithium is primarily excreted by the kidneys as a free ion.

Under normal circumstances, it is reabsorbed in the proximal tubule, and handled by the kidney like sodium.

Lithium is known to cause a number of adverse effects on the kidneys with therapeutic use (e.g., oliguria, polyuria, renal tubular acidosis, nephropathy, nephrogenic DI, decreased creatinine clearance, end-stage renal disease).

Many of the renal disease states induced by lithium make the kidneys more susceptible to retaining lithium and contributing to toxicity.

The mechanism by which lithium causes neurotoxicity is not known, but may be related to its transport through sodium ion channels or exaggerated therapeutic effects, which have also not been completely discovered.

Lithium concentrates in the thyroid and interferes with its metabolism, commonly causing hypothyroidism, which may be subclinical.

Epidemiology

Elderly patients are at greater risk of lithium toxicity due to decreased GFR.

Increased risk of hypothyroidism if lithium is combined with valproate or carbamazepine.

No difference in gender or race and predisposition to lithium toxicity.

Prognosis

SILENT is defined by new irreversible neurotoxicity after lithium discontinued for 2 months or more.

Cerebellar toxicity is the most common permanent neurotoxicity, possibly due to demyelination.

After lithium toxicity has resolved, renal impairment may persist.

Special considerations for nursing and allied health professionals.

NA

What's the evidence?

1. Description of the Problem

(Describes how the therapeutic effect of lithium in bipolar affective disorder relates to inositol.)

(Describes how the dopamine D1 receptor may play a role in lithium's therapeutic effect in bipolar affective disorder.)

(Investigated how gene polymorphism in serotonin receptor genes may play a role in lithium treatment for bipolar affective disorder.)

(Reviews and summarizes the vast and varied literature pertaining to lithium pharmacology and pharmacodynamics, including drug interactions.)

(Reviews the literature pertaining to brain lithium nuclear magnetic resonance spectroscopy and the findings when these brain concentrations are compared with serum lithium concentrations in therapeutic lithium use.)

(Describes elimination of lithium in a group of patients with lithium toxicity in whom hemodialysis was recommended but not performed.)

3. Diagnosis

(Studies the pharmacokinetics of lithium in two patients after massive intentional ingestions of sustained-release preparations.)

(Reviews 68 cases of lithium overdose and contrasts serum lithium levels and degree of toxicity in patients with acute and acute-on-chronic toxicity.)

(A study designed to determine a dose-response relationship between lithium and granulocyte production discovered that doses adequate to produce a serum lithium level of 0.55 mmol/L are sufficient to induce granulocytosis.)

(Describes a case of lithium toxicity associated with transient EKG abnormalities consistent with cardiac ischemia, but normal troponin and echocardiogram.)

4. Specific Treatment

(This in vitro study demonstrates that activated charcoal binds lithium in water, but they do not bind significantly in simulated gastric fluid.)

(In this small human study whole-bowel irrigation was shown to decrease the area under the lithium serum concentration curve and mean serum lithium concentration when administered 1 hour after a sustained-release lithium preparation.)

(A report of cases of lithium toxicity with a focus on toxicity in patients chronically on lithium and their renal function and unique requirements regarding treatment.)

(In this small human study healthy volunteers experienced decreased lithium absorption after a single dose of lithium followed by sodium polystyrene sulfonate, and no hypokalemia was noted.)

(Reviews 14 cases of lithium poisoning in patients who received hemodialysis, and comments on hemodialysis indications based on information obtained.)

(Reviews cases of lithium toxicity with and without hemodialysis after hemodialysis was recommended by a poison center, and while the result of withholding hemodialysis resulted in one death, other patients recovered without the therapy.)

(A case of lithium toxicity treated with hemodialysis and illustrates how serum lithium concentration does not correlate well with clinical signs of toxicity)

(Reviews a case of lithium toxicity in which both bicarbonate and acetate hemodialysis were utilized and compares the differences between the two types of dialysate in lithium toxicity.)

(Describes a case of lithium toxicity in which continuous venovenous hemodialysis was successfully used, including calculations of lithium clearance and serial serum lithium concentrations.)

5. Disease monitoring, follow-up and disposition

(Reviews cases of lithium toxicity with and without hemodialysis after hemodialysis was recommended by a poison center, and pharmacokinetics are characterized in lithium toxic patients without hemodialysis.)

(Reviews a large number of cases of patients with bipolar affective disorder with and without hypothyroidism and reports odds ratios of hypothyroidism associated with lithium, carbamazepine and valproate use.)

(Reviews the literature and makes recommendations regarding treatment of hypothyroidism in patients using lithium therapeutically.)